Download EXPERIMENT 3: Preparation and Reactivity of Alkyl Halides

Chemistry 283g-2007
EXPERIMENT 1: Preparation and Reactivity of Alkyl Halides
Relevant sections in the text: Fox and Whitesell: Chaper 7.4, 7.5, 8.1, 8.2, 8.3 (pg 386)
General Concepts
The most common of the variety of methods available for preparing alkyl halides is the
replacement of the hydroxyl group of an alcohol. This type of reaction is representative of an
important class of reactions in organic chemistry called nucleophilic aliphatic substitution
reactions. There are numerous ways of doing this transformation, and we will discuss these in
lecture. In this experiment you will convert an alcohol to an alkyl halide by reaction with a
hydrohalic acid. The overall reaction is shown in equation 1; however the mechanism of the
reaction depends on the structure of the alkyl group bearing the functional group being replaced.
R-OH + H-X  R-X + H2O
(1)
The reaction may occur by one of two mechanisms designated S N1 or SN2. Which mechanism
operates depends on the structure of the R group and the reaction conditions. The first step in
both mechanisms is the protonation of the alcohol to form an oxonium ion, converting the OH
group into a good leaving group. What happens next depends on the nature of the alkyl group, R.
If R is a group that readily forms a carbocation, then the slow, rate-determining step is the loss of
a water molecule from the oxonium ion. Once formed, the carbocation then reacts rapidly with a
halide ion to form the alkyl halide.
SN1 Mechanism:
The first step is protonation of the alcohol, followed by the second step which is the formation of
the carbocation via the oxonium ion. This second step is the slow step (rate-determining).
X
H
HO
R1
R2
R3
H
R4
R3
+ H2O
R1
R2
H2O+
R4
RDS
H
R3
R4
R1
R2
H
The third step is the attack of the planar carbocation by X- (in our case the halide ion).
X-
R3
R4
R1
R2
H
R1
R2
X
R3 R
4
H
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This mechanism is followed when R is a tertiary alkyl group and is called S N1 (substitution,
nucleophilic, unimolecular in the rate-determining step). An SN1 mechanism may also be involved
when R is a secondary group or when R can form a resonance-stabilized carbocation, such as an
allyl or benzyl cation. (The more stable the carbocation, the more likely the SN1 mechanism)
If R is a primary alkyl group, then substitution occurs generally without formation of the
carbocation by an SN2 mechanism (why no carbocation? Because 1o carbocations are generally
unstable). In this case a halide ion attacks the primary carbon atom of the oxonium ion in the ratedetermining step, and the alkyl halide forms directly. (why is this mechanism not favorable when
R = tertiary?) Because two species, the nucleophile (X -) and the substrate (the protonated
alcohol), are involved in the rate-determining step, the mechanism is designated SN2. When R is
a secondary group, an SN1 or an SN2 mechanism may be involved, depending on the reaction
conditions.
SN2 Mechanism:
H2 O
X
H
R
HO
H
H
R
H
R
+H O
2
H
H
R
H H
H
X
R
R
H
X
In this experiment you will prepare 1-bromobutane (1-butyl bromide) from 1-butanol. By what
mechanism do you expect this substitution reaction to occur? Compound 1-butanol is a primary
alcohol and thus one might expect that the reaction would proceed by an S N2 reaction. However,
when a strong, non-nucleophilic, acid is used as a solvent the conditions are very polar and the
reaction can proceed via an SN1 reaction. You will use the NMR spectrum of your product and
gas chromatography results to make decisions about which mechanism is operating.
NaBr / H2SO4
CH3CH2CH2CH2OH
CH3CH2CH2CH2Br
The purity of the product (and any possible side products) will be assessed by gas
chromatography and the identity of the product will be determined by IR, 1H, and 13C NMR
spectroscopy. You will also evaluate the reactivity of your product and other substrates using a
number of qualitative tests in Part B.
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Part A: Preparation of 1-bromobutane
Experimental Procedure

Place 20.0 g of sodium bromide in a 250 mL roundbottomed flask. Add 15 mL of water and 15 mL of 1butanol. Mix thoroughly and cool the flask in an ice
bath.

Slowly add 15 mL of concentrated sulfuric acid to
the solution. Remove the flask from the ice bath,
add a couple boiling chips, and attach a reflux
condenser.

Heat the flask with a heating mantle until most of the
salts have dissolved and the solution is at a gentle
reflux. Note the appearance of two layers (lower
layer is the alkyl bromide). Continue the reflux for 45
min.

Equip the flask for simple distillation with a heating
mantle. Distil the mixture rapidly into an ice-cooled
flask until the head temperature reaches 120C. Codistillation of 1-bromobutane and water occurs, and
the increased boiling point is due to the codistillation of sulfuric acid and hydrobromic acid with
water.

Transfer the distillate to a separatory funnel (with a closed stockcock!) and perform an
extraction. Add 25 mL of water to the organic layer in the funnel. Invert the funnel and point
into the fume hood and away from any other people. Remember to shake the funnel gently
with venting. Separate and label each layer carefully.

Wash the organic layer with 15 mL of saturated sodium bicarbonate solution and then again
with 15 mL of saturated sodium chloride solution. Collect the organic layers and discard the
aqueous layers.
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
Transfer the cloudy 1-bromobutane layer to a small Erlenmeyer flask, and dry it with
anhydrous magnesium sulfate. After allowing drying for about 10 minutes, gravity filter the
mixture into a clean, dry and tared (i.e. preweighed) 50 mL round-bottomed flask.

Determine the yield of crude product.

After adding a couple of new boiling chips, equip the flask for simple distillation again with a
heating mantle. Collect the product that comes off when boiling at 90-103 oC into a clean and
dry tared flask. Calculate the yield of the purified product.

Analyze your product by gas chromatography on a nonpolar column (SF-96 or SE-30 is
satisfactory). Obtain the retention times of standard samples of 1- and of 2-bromobutane.
Obtain an IR spectrum of your product and of 1-butanol and discuss the differences observed.
(you will likely have to add some drying reagent to remove traces of water). Prepare a sample of
your product for NMR analysis (as you did in Chem 273a experiment 3). You will be provided with
the relevant spectra of 1-butanol and the authentic NMR spectra of the two possible products.
Assign the signals as completely as possible and discuss the differences between the two
spectra. In your report discuss the relative percentages of 1- and 2-bromobutanes in your product
in terms of the mechanism(s) of the reaction. You will get this information by analyzing your GC
trace and your NMR spectrum of your product.
Gas Chromatography
Gas chromatography is a versatile and widely used method for the examination of volatile
mixtures by distributing each component in the mixture between a gas phase and either a liquid
or solid phase. The method can be used to follow the course of a reaction both qualitatively and
quantitatively, to separate and isolate components of a mixture, to examine purity, and to assist in
the identification of compounds.
The compound mixture is passed through a heated column (glass capillary tubing) as a
vapour, surrounded by an inert carrier gas. The column is coated with a stationary phase that
varies in type and structure depending on the type of separation required. The separation
process is readily understood in qualitative terms. Consider a two-component mixture entering
the column. Each component will be partitioned between the gas phase and the stationary liquid
phase depending on the volatility of the component and its affinity for the stationary phase. Since
each component will have a different distribution between the two phases, the most volatile/least
soluble in the stationary phase will be sent through the column more rapidly than the other, where
separation is achieved.
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Part B: SN1 and SN2 REACTIVITY
(i) Reactivity of Alkyl Halides Towards Sodium Iodide: Test for SN2
In this part of the experiment, you will test the reactivity of several alkyl halides in an SN2 reaction.
Iodide ion (I-) is an effective nucleophile in SN2 displacements. In acetone solution, other alkyl
halides (alkyl chlorides or bromides) can be converted to alkyl iodides easily by this method.
Although one might expect such a reaction to be reversible, it can be driven to formation of R-I by
using anhydrous acetone as the solvent. Sodium iodide (NaI) is soluble in this solvent, but
sodium chloride and sodium bromide are not. If a reaction occurs, a precipitate of sodium chloride
or sodium bromide forms and thus the ion is not available in solution for the reverse reaction. The
displacement mechanism involves a one-step, concerted, SN2 reaction. Therefore, the reaction
occurs most quickly when attack at the carbon that bears the halogen (X) is least hindered
sterically. For alkyl halides, the order of reactivity is primary > secondary > tertiary.
(ii) Lucas Test: Test for SN1
The reactivity of the product will be evaluated using the Silver Nitrate Test.
The Lucas Test will
also be used to distinguish the reactivity between various alcohols. The Lucas Test utilizes a
reagent containing hydrochloric acid and zinc chloride, which converts alcohols to alkyl chlorides.
Primary alcohols do not react, secondary alcohols react fairly quickly, and tertiary alcohols react
very rapidly.
A positive test depends on the fact that the alcohol is soluble in the reagent,
whereas the alkyl chloride is not; thus the formation of a second layer or an emulsion constitutes
a positive test. This is a good test for the feasibility of a particular alcohol to undergo an SN1
reaction. The overall reactions are as follows:
ZnCl2
Primary:
RCH2OH + HCl
Secondary :
R2CHOH + HCl
Tertiary:
R3COH + HCl
No reaction
ZnCl2
R2CHCl + H2O
ZnCl2
R3CCl + H2O
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(iii) Silver Nitrate Test: Test for SN1
The Silver Nitrate Test allows for the identification of alkyl halides by observing them in an
alcoholic silver nitrate environment. The rate at which the silver halide salt precipitate forms is
characteristic of different types of alkyl halides. You will test the reactivity of several alkyl halides
in a SN1 reaction. Organic halides may react with ethanol to form ethyl ethers. When the ethanol
contains silver ion, the rate of reaction increases because the silver ion acts as an electrophile
toward the halogen and helps to break the carbon-halogen bond. Alkyl chlorides yield an
observable silver chloride precipitate, which is insoluble in ethanol and thus provides a indicator
that a reaction has occurred.
R-Cl + CH3CH2-OH + Ag+

CH3CH2-OR + AgCl (ppt) + H+
In this case, the reaction mechanism is SN1, the slow step being the breaking of the carbonhalogen bond. The carbocation then reacts rapidly with alcohol to form the ether.
Organic halide reactivity parallels the stability of the corresponding carbocations. For saturated
alkyl groups, this order is tertiary > secondary> primary. Tertiary, allylic, and benzylic alcohols
react very quickly, while secondary alkyl halides react fairly quickly. Primary as well as aryl,
alkenyl (vinyl), and alkynyl halides do not react at all. In addition, alkyl iodides and bromides
react faster than chlorides, which sometimes require heating.
Experimental Procedures Part B:
IMPORTANT! Clean dry test tubes from oven must be used for these tests. Tests are to
be performed in the fume hood; whenever transporting your test tube ensure they are
safely stoppered with a cork.
(i) Sodium Iodide Test: SN2 Reactivity
Test each of the following organic bromides: 1-bromobutane, 2-bromobutane, 2-bromo-2methylpropane (tert-butylbromide), allyl bromide (3-bromopropene), bromobenzene and your
product from Part A.

Dry test tubes must be used for this experiment. Use the disposable small test tubes.

Add 2 drops of the liquid to be tested to 1 mL of a 15% solution of sodium iodide in
dry acetone. Mix the contents and note the order of reactivity by looking at how
long it takes for a precipitate to form. The solution may turn slightly yellow – this is
NOT due to the SN2 reaction. (Hint: SN2 reactions are slower than SN1 reactions. Save
your test-tubes for 45-60 minutes and check occasionally for any changes before
discarding).
Tabulate the results of your qualitative tests including detailed observations. Discuss the results
in terms of the reaction mechanism.
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(ii) Lucas Test: Reactivity of Alcohols
Conduct the test on each of the following alcohols: methanol, ethanol, 1-butanol, 2-butanol, 2methylpropan-2-ol (tert-butanol) and benzyl alcohol.

Add ~1 mL of the hydrochloric acid-zinc chloride reagent (Lucas reagent) to 4-5 drops of the
alcohol compound in a small clean and dry test tube.

Stopper the tube, shake, and note any change observed. Also record the time required for
the formation (if any) of an alkyl chloride (second layer or an emulsion).

If no reaction is observed after 5-10 min at room temperature, heat gently using a steam bath
for 2-3 min.
Tabulate the results of your qualitative tests including detailed observations. Discuss the results
in terms of the reaction mechanism.
(ii) Silver Nitrate Test: Reactivity of Alkyl Halides
CAUTION: Avoid skin contact with the silver nitrate solution. It will form a dark, hard-toremove stain where it comes into contact with skin.
Conduct the test on each of the following alkyl halides: 1-bromobutane, your product, 1-bromo-2methylpropane (iso-propyl bromide), 2-bromo-2-methylpropane (tert-butyl bromide), benzyl
bromide, and bromobenzene.

Add 1 drop of the alkyl halide to 2 mL of a 0.1 M solution of silver nitrate in 95% ethanol in a
small test tube. Stopper, shake, and note any change (and time required).

If no reaction is observed within 5 min at room temperature, warm the mixture in a steam
bath and observe any change.

When noting the color of any precipitate, keep in mind that silver chloride is white, silver
bromide is pale yellow, and silver iodide is yellow.

Add several drops of 1 M nitric acid solution to any precipitate, and note any changes.
If the precipitate remains, it is a silver halide. Silver halides are insoluble in acid, while the silver
salts of organic acids are soluble. Also, silver hydroxide (oxide) is insoluble but dissolves in dilute
acid. Tabulate the results of your qualitative tests including detailed observations. Discuss the
results in terms of the reaction mechanism.
At the end of the laboratory please be sure your clean test tubes are placed in the oven for
your colleagues.
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